BNT162b2 mRNA 疫苗在体外和体内都能降低年龄相关的 TH1 支持率

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2024-11-15 DOI:10.1016/j.isci.2024.111055

Byron Brook , Abhinav Kumar Checkervarty , Soumik Barman , Cali Sweitzer , Anna-Nicole Bosco , Amy C. Sherman , Lindsey R. Baden , Elena Morrocchi , Guzman Sanchez-Schmitz , Paolo Palma , Etsuro Nanishi , Timothy R. O’Meara , Marisa E. McGrath , Matthew B. Frieman , Dheeraj Soni , Simon D. van Haren , Al Ozonoff , Joann Diray-Arce , Hanno Steen , David J. Dowling , Ofer Levy

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The BNT162b2 mRNA vaccine demonstrates reduced age-associated TH1 support in vitro and in vivo

mRNA vaccines demonstrate impaired immunogenicity and durability in vulnerable older populations. We hypothesized that human in vitro modeling and proteomics could elucidate age-specific mRNA vaccine actions. BNT162b2-stimulation changed the plasma proteome of blood samples from young (18-50Y) and older adult (≥60Y) participants, assessed by mass spectrometry, proximity extension assay, and multiplex. Young adult up-regulation (e.g., PSMC6, CPN1) contrasted reduced induction in older adults (e.g., TPM4, APOF, APOC2, CPN1, PI16). 30–85% lower T_H1-polarizing cytokines and chemokines were induced in elderly blood (e.g., IFNγ, CXCL10). Analytes lower in older adult samples included human in vivo mRNA immunogenicity biomarkers (e.g., IFNγ, CXCL10, CCL4, IL-1RA). BNT162b2 also demonstrated reduced CD4⁺ T_H1 responses in aged vs. young adult mice. Our study demonstrates the utility of human in vitro platforms modeling age-specific mRNA vaccine immunogenicity, highlights impaired support of T_H1 polarization in older adults, and provides a rationale for precision mRNA vaccine adjuvantation to induce greater immunogenicity.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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